Project Summary Optical coherence tomography angiography (OCTA) has been introduced recently as a non- invasive, 3-dimensional imaging method to visualize and quantify microvasculature throughout the retina. The proposed study evaluates the clinical utility of OCTA measurements compared to standard structural measurements of the optic nerve head (ONH), retinal nerve fiber layer (RNFL) and macula measured using the current clinical imaging standard, spectral domain optical coherence tomography (SDOCT). Our research, and that of others, has shown that superficial retinal vessel density (proportion of measured area composed of blood vessels) in the ONH region and macula is less dense in primary open angle glaucoma (POAG) eyes than in healthy eyes. Moreover, diagnostic accuracy is improved with increasing disease severity. Research from our laboratory suggests that the diagnostic accuracy of vessel density is similar to that of SDOCT-measured RNFL thickness, and that vessel density is reduced in retinal regions associated with localized visual field (VF) defects. These cross-sectional results strongly suggest that OCTA measurements reflect damage to tissues relevant to the pathophysiology of POAG. In a longitudinal study, moreover, the mean rate of change in macula vessel density is significantly faster in POAG eyes than in glaucoma suspect or healthy eyes. The current study provides a unique opportunity to extend for up to 8 years longitudinal OCTA data that has already been collected from 250 eyes over 2 years, and to investigate vessel density change over time in glaucoma suspect and POAG eyes, as well as to compare it to other imaging modalities and glaucoma-related visual field change. The aims of the study are 1) to assess the longitudinal temporal and topographic relationship in glaucoma between loss of superficial retinal vessel density, loss of RNFL thickness, loss of neuroretinal rim width, and loss of ganglion cell complex (GCC) thickness in glaucoma suspect and glaucoma eyes of varying disease severity, and 2) to assess the longitudinal temporal and topographic relationship between superficial loss of macula and ONH retinal vessel density, loss of RNFL thickness , loss of neuroretinal rim width, and loss GCC thickness with the development and progression of central and peripheral VF defects in glaucoma. Comparison of the time course of changes in vessel density relative to changes in RNFL thickness, neuroretinal rim width, ganglion cell layer thickness and visual function will provide information about the pathophysiology of glaucoma that can improve early detection and accurate monitoring of advanced disease compared to currently available and widely accepted methods. Enhanced diagnosis and detection of progression should lead to earlier and more effective treatment, thus reducing the rate of disease worsening and preventing loss of vision-related quality of life (including blindness).